The purpose of this application is to study the activation of resting, antigen-specific virgin and memory B cells by two types of helper T cells (Th1 and Th2). The first part of the proposal will investigate the events occurring during "conjugation" of antigen-specific B cells (that have processed antigen) and The cells. These events will include the identification of gap junctions, and the transfer of mediators and/or lymphokines between the two cells. In addition, we will determine if only those antigen-specific B cells that conjugate to the T cells in an antigen-specific, MHC-restricted fashion differentiate into antibody-secreting cells. The second part of the application will address the question of which B cells are activated by each type of The cell (Th1 and Th2) and the role of T cell-derived lymphokines produced by these The cells during T/B interaction. Finally, we will test a model of T/B interaction leading to B cell activation by adding, sequentially, antigen, different types of antigen-specific The cells (Th1 or Th2) or purified lymphokines (IL-4, IL-2, gamma-IFN, etc.) to resting, antigen-specific B cells.